Severe mucosal Candida albicans is a major cause of morbidity and mortality in immunosuppressed individuals and less toxic therapeutic agents are needed. Our collaborator, Dr. Luciano Polonelli has prepared a number of yeast killer toxin (KT) anti-idiotype antibodies (KT-ID Mab) that mimic the cytotoxic activity versus Candida and Pneumocystis of the native killer toxin. Native KT Cannot be used because it is unstable, immunogenic and has much reduced activity at neutral pH. The KT-ID Mab applied topically in rodent models was effective versus both vaginal candidiasis and pulmonary P. carinii infections. The plant molecular biology unit of Panorama Research Inc. (PRI) has pioneered proprietary methods for the production of secretory lgA antibodies in transgenic plants. SigA plantibodies are the preferred form of antibody therapy for mucosal use. The overall goal of the present project is to prepare an SIgA form of this anti-ID as an economical, stable, therapeutic for C. albicans infection. In phase I we will construct secretory IgA plantibody expression cassettes using the bioactive scFv having demonstrated candidacidal activity. These will be used to transform tobacco by particle bombardment and plants expressing assembled SIgA will be selected. Next we will demonstrate cytotoxic activity of the purified anti-ID SIgA plantibody using in vitro candidacidal assays. Successful completion of this project will demonstrate a general proprietary method to combat difficult mucosal pathogens. PROPOSED COMMERCIAL APPLICATIONS: Severe mucosal candidiasis infections are a major problem. A novel therapeutic represents a significant market opportunity.